Pyrido pyrimidine 3-oxide, reaction

Oxidation of Oximes A different type of N-oxidation reaction involves the direct oxidation of oximes to nitro compounds. Although a variety of oxidizing agents have been described for this reaction, the use of non-heme iron-based systems is rather limited. In this context, the oxidation of the oxime group in tetrahydro-4H-pyrido[ 1,2-a]pyrimidines was carried out at room temperature in the presence of 50 mol% of Clayfen [K10 montmorillonite-supported iron(III) nitrate] (Scheme 3.45) [147]. Under these conditions the corresponding nitro derivatives were obtained in 32-35% yield. 1SN mass studies revealed that the reaction involved the direct oxidation of the hydroxyimino group. 

Cycloaddition reactions of electron rich 6-[(dimethylamino)methylene] aminouracil with various electron deficient substrates gives pyrimido[4,5-d]pyrimi-dines and pyrido[2,3-d]pyrimidines. This reaction takes place in two steps, firstly formation of cycloadducts and then elimination of dimethylamine from the cycloadducts and oxidative aromatization (Gohain et al, 2004). The reaction gives excellent yields, when carried out under microwave irradiation and solvent-free conditions. 

Pyrido[3,2-d]pyrimidine, 2-arylthio-oxidation, 3, 211-212 Pyrido[3,2-d]pyrimidine, 4-bromo-reactions, 3, 215... 

Reaction of 2-(A -allylamino)-3-formyl-4//-pyrido[l, 2-u]pyrimidin-4-ones 219 in EtOH with HONH2 HCI yielded ( )-oximes 220 at 0°C and 221 (R = PhCH2) under reflux. Heating 220 (R = H) in a boiling solvent afforded cw-fused tetracyclic cycloadducts 221 (R = H). In an aprotic solvent (e.g., benzene or MeCN) the main a>fused cycloadducts 221 (R = H) were accompanied by a mixture of trauA-fused cycloadducts 222, A -oxides 223 and tetracyclic isoxazoline 224 (96T887). The basicity of the 2-allylamino moiety of compounds 219 affected the rate of the conversion. Cycloadditions were also investigated in dioxane and BuOH. 

The reaction of pyrido[2,3-c/]pyrimidine-3-oxide (415) and diethyl malonate in the presence of sodium ethylate in ethanol at 0°C for 10 min led to the formation of Af-[3-(l,2,4-oxadiazol-3-yl)-2-pyridyl]aminomethylene-malonate (416) in 73% yield, but at ambient temperature for 1.5 hr, the product was diethyl N-(3-cyano-2-pyridyl)aminomethylenemaIonate in 61% yield (83JOC4132). 

Some unusual syntheses of substituted 2,2 -bipyridines deserve mention. Tetracyclone (tetraphenylcyclopentadienone) on heating with picolinonitrile at 215°C affords 3,4,5,6-tetraphenyl-2,2 -bipyridine, whereas 5-methyl-2,2 -bipyridine and some polysubstituted 2,2 -bipyridines are obtained by the oxidative degradation of the antibiotic streptonigrin. 5-Aldehydo-6-amino-2,2 -bipyridines are obtained by acid hydrolysis of pyrido[2,3-[Pg.311]

Microwave-assisted multicomponent reaction of 6-amino- or hydroxy-aminouracil derivatives with benzaldehyde and malononitrile or ethyl cyanoacetate in the solid state in the absence or presence of Et3N for 5-8 min afforded the pyridopyrimidine derivatives 463 <2003TL8307>. Similarly, 6-aminouracil derivatives or 6-hydroxyamino analogues were reacted with HC(OEt)3 and active methylene compounds [CH2(CN)2 or NCCH2C02Et] in the presence of AcOH under microwave-assisted conditions to give the pyrido[2,3-r7 pyrimidines 464 and their iV-oxides 465 within 2 or 8 min, respectively. The reaction proceeded under thermal conditions in ethanol or without solvent for 1—4h to give 464 and 465 in 45-70% and 35-50% yield, respectively <2004SL283>. 

Al-Jallo and Al-Biaty24 prepared 4-phenyl-2-oxo-2H-pyrido[l,2-c<]-pyrimidines from 2-aminopyridines and ethyl phenylpropiolate. When the reactions were carried out in deuterium oxide, the 3-deuterated derivatives were obtained. 2-Amino-5-nitropyridine failed to react. 

Mohrle and Mayer240,241 oxidized the 3-piperidinopropylamine (182) with mercuric acetate-EDTA reagent to obtain the pyrido[l,2-u]pyrimidine (184). Oxidation of the N-monomethyl and N,JV-dimethyl derivatives of 182 resulted in the N-methyl and A,A-dimethypiperidone derivatives of 185.241 If the reactions were carried out without the addition of EDTA, the perhydropyrido[l,2-a]pyrimidine(l83) and its N-methyl derivative also could be isolated from the reaction mixture.241 The pyrido[l,2-a]pyrimidine (184) was also prepared from the piperidone (186).242 The oxidative cyclization was successfully when applied to the piperidinopropionamides (187) to prepare the pyrido[l,2-a]pyrimidines(188) in addition to 2-oxopiperidino-propionamides.243... 

Within the following subsections the stability of the bicyclic ring system, plus the hydrogenation, reduction, dehydrogenation, oxidation, and quater-nization of the compounds are reviewed. This is followed by discussion of substitution reactions affecting the pyrido [ 1,2-a]pyrimidine ring, transformations of the side chains, and finally ring transformation reactions. 

On treatment of a solution of the pyrido[l,2-a]pyrimidinium salt (16) with potassium permanganate in 2 N sulfuric acid, 11% 2-aminopyridine, 1% 4-oxo-4H-pyrido[l,2-a]pyrimidine, and traces of 2-nitropyridine were isolated from the reaction mixture.9 When 2,4-dimethylpyrido[l,2-a]-pyrimidinium iodide was oxidized with aqueous potassium permanganate at 50-60°C, 2-acetamidopyridine was obtained in 65% yield.2... 

If the reaction of 9-halo-4-oxo-6,7,8,9-tetrahydro-4tf-pyrido[l,2-a]pyri-midines and amines was carried out in the absence of air, the 9-amino-4-oxo-6,7,8,9-tetrahydro-4if-pyrido[l,2-a]pyrimidines were isolated, which could be oxidized by air to the 6,7-dihydro analogs.308 The latter were directly prepared from 9,9-dihalo-4-oxo-6,7,8,9-tetrahydro-322 or 9-hydroxy-4-oxo-6,7-dihydro-4A/-pyrido[l,2-a] pyrimidines308 with amines. 

Perhydropyrido [ 1,2-a]pyrimidine was oxidized with the mercuric acetate-EDTA complex. When the reaction mixture was treated with potassium carbonate, 3,4,6,7,8,9-hexahydro-2//-pyrido[l,2-a]pyrimidine was obtained, whereas on work-up with 20% sodium hydroxide the product was l-(3-aminopropyl)-2-oxopiperidine.344... 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Formyl derivative 362 was prepared when 9-hydroxymethylpyrido-pyrimidin-4-one 361 in dichloromethane was added to a cooled mixture of oxalyl chloride and dimethyl sulfoxide at - 50°C/ - 60°C in the presence of triethylamine. 9-Formyl derivative 362 was oxidized with silver nitrate in aqueous ethanol, and after 15 minutes of stirring the reaction mixture was treated with aqueous potassium nitrate for 2 hours at ambient temperature to give pyrido[ 1,2-a]pyrimidine-9-carboxylic acid 363 (91EUP453042). 

The reaction of 9-mercapto-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carboxylates 513 (R1 = COOEt) and nitrile oxides in methylene chloride in the presence of trimethylamine at -20°C, then at ambient temperature for 24 hours, afforded 9-substituted pyrido[l,2-a]pyrimidine-3-carboxylates 521 (89EUP329126). 

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